ProMIS (PMN) Q3 2026 Earnings Call Transcript

Image source: The Motley Fool.

DATE

Thursday, Nov. 12, 2026

CALL PARTICIPANTS

• Vice President of Investor Relations and External Affairs - Carrie Pierce
• President and Chief Executive Officer - Neil K. Warma
• Chief Medical Officer - Larry Douglas Altstiel

Need a quote from a Motley Fool analyst? Email pr@fool.com

TAKEAWAYS

• Cash -- $44.1 million as of Sept. 30, 2026, representing an increase from $6.1 million at the end of 2025 due to a private placement.
• Research and Development Expenses -- $6.7 million for the quarter, reflecting a 32% decrease from $9.8 million in the third quarter of 2025.
• Net Loss -- $8.2 million, or $0.89 per share, compared to $11.6 million, or $5.93 per share, in the prior year period.
• ARIA-E Incidence -- 0% as of the six-month interim analysis, spanning all APOE genotypes including homozygotes.
• ARIA-H Incidence -- 4.4% as of the interim cutoff, characterized by management as mild, asymptomatic, and in line with placebo rates.
• Plasma p-tau217 -- Approximately 15% reduction from baseline, observed in pooled, blinded interim data from the Phase 1b trial.
• CSF MTBR-tau243 -- Approximately 13.3% decrease from baseline, indicating potential target engagement within the central nervous system.
• Topline Data Target -- First quarter of 2027, which will include 12-month unblinded results for safety, biomarkers, and clinical efficacy.
• Target Clinical Efficacy -- 15% to 20% directional slowing of decline on iADRS or CDR-SB, which management noted would be similar to effects seen in marketed therapies.
• Trial Enrollment -- 144 total patients enrolled in the Phase 1b PRECISE AD study, with 136 evaluable for safety as of the latest report.
• APOE4 Genetic Distribution -- 11% APOE4 homozygotes within the evaluable patient population, a group typically at higher risk for side effects.
• Subcutaneous Formulation Timeline -- Late 2027 for a potential registration study start, pending feedback from the FDA.
• Cash Runway -- Extension through 2027, which the company stated is sufficient to fund operations beyond the upcoming topline data readout.
• General and Administrative Expenses -- $1.9 million for the quarter, remaining relatively flat compared to $2.0 million in the same period last year.
• PMN310 Direct Cost Reduction -- $3.6 million, driven by the PRECISE AD trial moving toward the completion of patient visits.
• Nine-Month Net Loss -- $28.1 million, or $3.39 per share, compared to $29.0 million, or $19.58 per share, for the first nine months of 2025.
• Other Income -- $500,000 for the quarter, up from $200,000 in the prior year period, primarily due to higher interest income on cash balances.
• Weighted-Average Outstanding Shares -- 9.1 million basic and diluted shares for the quarter, compared to 2.0 million basic and diluted shares in the third quarter of 2025.
• Phase 1a Target Engagement -- Dose-dependent reduction in detectable amyloid-beta oligomers, as demonstrated in healthy volunteer studies.
• Study Randomization -- 3-to-1 active-to-placebo ratio, utilized in the 140-patient blinded interim analysis.

SUMMARY

ProMIS Neurosciences, Inc. (NASDAQ:PMN) reported progress on its lead Alzheimer’s candidate, PMN310, as the company nears the completion of its Phase 1b PRECISE AD clinical trial. Management stated that patient visits are expected to conclude in the fourth quarter of 2026, with unblinded 12-month topline results scheduled for the first quarter of 2027. The company's financial position was strengthened by a $70.1 million private placement earlier in the year, providing a cash runway through 2027. ProMIS remains focused on demonstrating the safety and efficacy advantages of its oligomer-selective approach compared to currently approved therapies that show higher rates of brain swelling and require intensive monitoring. The clinical strategy includes the parallel development of a subcutaneous formulation to improve patient compliance and reduce the need for recurring imaging surveillance.

• Neil Warma noted that recent competitor failures "sharpen rather than weaken the case for PMN310" due to differences in selectivity and safety profiles.
• Management reported that PMN310 uses an IgG1 backbone designed to engage microglia and actively clear toxic oligomers through neutralization and clearance.
• The company announced the appointment of Dr. Ivana Rubino as chief commercial officer to guide regulatory and late-stage development strategies.
• Dr. Larry Altstiel indicated that the Phase 1b study will utilize a new, highly sensitive assay to measure absolute concentrations of amyloid-beta oligomers in cerebral spinal fluid.
• Management stated that the reduction of ARIA risk could "dramatically reduce the need for repeated MRI monitoring," addressing a primary barrier to broader treatment adoption.
• The company intends to request an end of phase two meeting with the FDA after the full set of 12-month data is analyzed next year.

INDUSTRY GLOSSARY

• Amyloid-beta: A protein that can misfold and form plaques or toxic oligomers in the brain, associated with Alzheimer's disease.
• ARIA (Amyloid-Related Imaging Abnormalities): Brain swelling (ARIA-E) or hemorrhage (ARIA-H) often associated with amyloid-clearing therapies.
• p-tau217: A blood-based biomarker linked to the presence of amyloid plaques and the progression of Alzheimer's disease.
• MTBR-tau243: A cerebrospinal fluid biomarker that reflects the presence of tau tangles in the brain.
• CDR-SB (Clinical Dementia Rating-Sum of Boxes): A numerical scale used to quantify the severity of dementia symptoms.
• iADRS (Integrated Alzheimer's Disease Rating Scale): A composite clinical tool measuring both cognitive and functional decline in patients.
• APOE4: A genetic variant that represents the strongest genetic risk factor for late-onset Alzheimer's disease.

Full Conference Call Transcript

Operator: Good afternoon, and welcome to the Promise Neuroscience's third Quarter 26 Financial Results and Corporate Update Conference Call. At this time, all participants are in a listen-only mode. As a reminder, this call is being recorded. I would now like to turn the call over to Carrie Pierce, Vice President of Investor Relations and External Affairs. Please go ahead.

Analyst: Thank you, operator, and good afternoon, everyone. Earlier today, Promise issued a press release announcing our financial results for the third quarter ended 09/30/2026. And provided a corporate update. The press release is available on the section of our website and on our quarterly report on Form 10 Q and has been filed with the SEC and on SEDAR plus. Please join me on today's call are Neil K. Warma, our President and Chief Executive Officer, who will deliver our prepared remarks and Dr. Larry Altstiel, our Chief Medical Officer, who will be available during the Q&A session.

Before we begin, I would like to remind everyone that today's call will include forward looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 and applicable Canadian securities laws. These include, among others, statements regarding our clinical development plan and timelines for PMN310 and other product candidates the interpretation and significance of the blinded interim data from our PRECISE AD trial our expectations regarding future clinical results, the timing of top line data, our financial position and cash runway and our overall business strategy.

These statements are based on management's current expectations and are subject to risks and uncertainties that could cause actual differ from actual results materially, including the risks that early or interim results may not be indicative of final or top line results. Please refer to the risk factors section in our most annual report on Form 10-K and our subsequent filings with the SEC. Including our quarterly report on Form 10 Q and for the quarter ended 09/30/2026. These statements speak as of today, 11/12/2026, and we undertake no obligation to update them except as required by law. With that, I will turn the call over to Neil.

Neil K. Warma: Thank you, Carrie. Good afternoon, everybody, and thank you for joining PROMIS is entering probably the most important period in its history. Our phase 1b study, PRECISE AD, in clinical. In Alzheimer's disease, is nearing completion. All patient visits are expected to conclude this quarter and unblinded 12 months top line data remain on track for the first quarter of 2027. Today, I want to focus on 4 things.

Why recent events in the field sharpen rather than weaken the case for PMN310, the strength of the interim data from July, that we have seen in our PRECISE AD trial, how we will judge the top line results, coming shortly and how we are positioned both strategically and financially to move efficiently once we have the data. First, I wanna directly address the phase 2 results reported 2 weeks ago by another company developing an antibody described as oligomer selective. That trial did not meet its primary or secondary endpoints at 18 months. And we have looked closely at the limited data that were disclosed And 2 key findings really stand out to us.

First, that the antibody produced statistically significant reductions in amyloid plaque on PET at both doses and second approximately 10% of treated patients developed ARIA E or brain swelling. In our view, both of those findings indicate meaningful engagement of plaque amphibular amyloid, not selective targeting of oligomers. And that matters. A molecule that clears plaque and causes aria is behaving much like the existing plaque directed drugs. So in our view, that trial did not test the oligomer hypothesis. Selectivity is not a label. It has to be demonstrated both at the bench and in patients. And this is precisely where we believe PMN310 is different and the data we have to date support that view.

The field still needs a clinical test of oligomer selective targeting. We believe PRECISE AD will be that test. Let me explain a little what sets PMN310 apart. PMN310 our lead candidate, lead antibody, was built around 1 hypothesis. That toxic amyloid beta oligomers drive neurodegeneration in Alzheimer's disease. And that selective neutralizing and clearing them can deliver benefit without the safety burden of plaque directed therapies. 3 key features set PMN310 apart. Number 1, selectivity. In head to head preclinical studies, PMN310 was the only antibody tested that bound toxic oligomers, while avoiding monomers avoiding fibrils, and avoiding plaque. Other antibodies include those described as oligomer selective, consistently showed binding to plaque.

And additionally, the interim results from our phase 1b study presented last July or this past July have reaffirmed our confidence in PMN310's selective profile. Number 2 is design. Like the 2 approved antibodies, PMN310 is built on an IgG1 backbone to engage microglia and actively clear toxic oligomers from the brain. We deliberately chose both neutralization and clearance. And number 3 is safety. By avoiding plaque, PMN310 is designed to reduce the risk of ARIA, which is still the single greatest barrier to broader use of anti amyloid therapy. At our 6-month interim analysis, PRECISE AD showed no ARIA-E, 0 cases of ARIA-E in any APOEG, APOE genotype.

And that is meaningful because with the approved antibodies, most ARIA occurred within the first 6 months of treatment. Though the interim read, to be clear, is not definitive, but it gives us real confidence going forward. The burden of ARIA goes beyond the brain swelling and bleeding it causes. To monitor for it, patients on the approved therapies must undergo as many as 6 MRI scans in their first year of treatment. And keep in mind, these are cognitively impaired patients and every scan is a real physical and financial burden on them, their caregivers, and the health care system.

So our goal with PMN310 is to reduce the incidence of ARIA, and with it, dramatically reduce the need for repeated MRI monitoring. Should PMN310 deliver ARIA rates at or near placebo, with efficacy at least as comparable to existing therapies, we believe it could become a leading treatment for early Alzheimer's disease and even open the door to preclinical asymptomatic patients where safety is absolutely paramount. And just as a reminder to the audience, the blinded 6-month interim analysis of 136 patients randomized 3-to-1 active to placebo, that we reported July 20 eighth of this year. Gave us an encouraging early read.

There were no ARIA-E cases in any APOE genotype, as of our cutoff date, ARIA-H at a rate of 4.4%. All mild and asymptomatic very much in line with placebo rates. There were no drug related discontinuations no treatment related serious adverse events. And on the target engagement, potential drug effect side, we demonstrated pool plasma p-tau217. Decreased approximately 15% from baseline and CSF MTBR tau 243. Decreased approximately 13%. From baseline. And remember, these are blinded, pooled observations and not a determination of efficacy. But they are consistent with target engagement and the safety profile is what we would expect from a true oligomer selective antibody.

Although no head to head studies have been conducted, our interim safety profile really stands in clear contrast to the ARIA rates seen in the recent competitor trial, and also with approved therapies. And let's turn for a minute. Let me turn to what we would consider a win when the top line data readout. In Q1 next year. Every Alzheimer's therapy is ultimately judged on its balance of benefit and risk. As weighed by the FDA, by prescribing physicians, by patients and their families. Today, that balance is a difficult 1. The approved antibodies offer a modest slowing of decline at the cost of ARIA risk and an intensive MRI schedule. Our goal is to shift that balance decisively.

PMN310 is designed to do that by lowering the risk side of the balance, while preserving the benefit. Efficacy comparable to the approved therapies with a clear safety advantage which shifted meaningfully. Any efficacy above what we see with the marketed drugs would shift it even further At top line, we will evaluate the totality of the data against that goal really looking at 4 things. With respect to safety, we are looking for ARIA, drug related adverse events, event rates approaching, or comparable to placebo rates. Clinical efficacy, we want to see a directional slowing of decline on either the iADRS or CDR Sum of Boxes versus placebo similar to approved therapies, at the 12 months, time point.

Biomarkers we would like to see changes that align with PMN310's oligomer targeted mechanism. So directional trends in line with our oligomer selectivity mechanism of action. And then with respect to mechanism of action, we would like to show direct changes in oligomer levels, following treatment with PMN310. And if PRECISE AD, if our clinical trial demonstrates a shift a material shift in the benefit risk profile, we believe there would be a significant value creating event for promise and a very meaningful step forward for patients. So I wanna take a minute now just to talk about how we are preparing for what comes next.

So we are not waiting--not sitting and waiting for top line data to come to plan the next phase. With fast track designation already in hand, we intend to request a meeting with FDA after the full set of data is analyzed. And in parallel, we are developing a subcutaneous formulation of PMN310 and preparing for a potential registration study, which we could envision beginning towards the end of 2027. Subject to FDA feedback, of course. We have also strengthened the team for that next phase, As we reported on October 5th, Dr. Ivana Rubino, joined the PROMISE team as chief commercial officer.

Ivana brings more than 15 years of global neuroscience and Alzheimer's leadership from senior roles at Biogen, and at Roche. And she will help shape our regulatory late stage development and commercial strategy. And attracting someone of Ivana's caliber, I think, speaks volumes to the potential of PMN310 and our overall platform. And on that note, while we have a strong pipeline, of selective antibodies for other serious neurodegenerative diseases, with high unmet medical need, and this includes ALS, Parkinson's disease, dementia with Lewy bodies, I have focused today's call on our commitments to the Alzheimer's patients and their caregivers and really around the enthusiasm we have for PMN310 and the upcoming data release.

So before we kind of jump into a questions and answers, I just want to turn briefly to our financial results. For the quarter. We ended Q3 with approximately $44.1 million in cash, which we expect to fund operations through 2027 well beyond the PRECISE AD readout. And you can find full details of our financials in our press release and our Form 10 Q that was filed today. Research and development expenses were approximately $6.7 million down 32% from the $9.8 million from a year ago. The decrease was really driven by a $3.6 million reduction in direct PMN310 costs, as the PRECISE AD trial moved towards completion.

This is partially offset by more activity in our ALS and pipeline programs. G&A, or general and administrative expenses were approximately $1.9 million which is roughly flat with the $2 million from last year. Other income rose about $500,000 from $200,000 on higher interest income. Net loss overall for the quarter was $8.2 million or $0.89 per share, and that is compared with $11.6 million or $5.93 per share from a year ago. For the first 9 months, net loss was roughly $28.1 million or $3.39 per share versus $29 million or $19.58 per share in 2025.

So just before we jump into the Q and A, just to summarize, recent events in the field, 1 that really made 1 thing more clear. Targeting oligomers is only as meaningful as the selectivity behind it. PMN310 was designed for that selectivity, and our interim data to date in the lab and in patients fully support our hypothesis. We have encouraging interim safety and biomarker data, a strengthened leadership team, and a balance sheet that funds us through 2027.

Our next catalyst is unblinded 12 month top line data from the PRECISE AD trial, expected in the first quarter of 27 And the question it will answer is whether PMN310 shifts the benefit risk balance in favor of patients with Alzheimer's disease. So on that note, I am now joined many of you know, our Chief Medical Officer, Dr. Larry Altstiel. So I am joined by Larry to answer questions coming through from the audience. So, operator, I would like you to please open the line and Larry and I will take questions from the group. Thank you.

Operator: We will now be conducting a question and answer session. If you would like to ask a question, please press *1 on your telephone keypad. A confirmation tone will indicate to remove your question from the queue. Thank you. Our first question comes from the line of Yatin Suneja with Guggenheim. Please go ahead.

Yatin Suneja: Thank you for taking my question. regarding the update. Neil, I think you just started talking or recently have started talking about what constitute a signal on the efficacy front. In fact, you have that also in the deck. So, you know, it would be great to maybe, you know, talk about that a little bit, also put in perspective the size of the study you are running relative to you know, what we have seen in a much larger study. I think it will be good for our investor to sort of understand that dynamic as well. Thanks.

Neil K. Warma: Yeah, of course. Thanks, Yatin. Thank you for the question. Yeah. it is interesting. We get. We do get. Obviously get questions around expectations around the trial. I kind of hinted at that in the, in the script here in talking through it. But what constitutes. You know, what is our target you know, our target goal here with the PRECISE AD trial. And as I mentioned here, we are really focused on the benefit risk profile. Do not mean to overemphasize that, but it really is important looking at both the you know, the risk side of the equation, so the safety versus the benefit side or the or the efficacy.

And our goal here, as we just went through, is to shift or alter meaningfully that benefit risk profile. So our expectations in this trial, and as I think we have said before, the best decision we made was in the design of this trial, and Dr. Altstiel sitting beside me, is responsible for that, in a good way, a very comprehensive phase 1b study. So, again, although it is comprehensive, it is 1b. We are looking at multiple endpoints. With respect to biomarker safety. Clinical outcome measures, and even mechanism of action around the oligomer. Reductions. You know, we wanna emphasize as well that this is a 140-patient study over 12 months.

So direct comparisons with the larger 18 month study in 1500 patients, we have to be careful putting that into context. But I think for us, for expectations coming out, the other side of this trial in Q1, if we could see safety approaching or close to that kind of background or placebo rate, especially around the ARIA-E. I mean, the ARIA, the burden of ARIA, as we mentioned, to patients and caregivers is significant. And that really, as we said, is the single thing restricting the uptake of the marketed drugs. So. And we have heard this from prescribing physicians. We have heard this from pharma companies.

If we, with PMN310, can dramatically alter the safety profile reduce ARIA levels, at or close to placebo or background rates, that would be a significant win. And on the other side of the equation, with the benefit, the efficacy, if we could you know, at least maintain similar efficacy. So when kind of looking at some of those numbers.

And, again, we wanna be careful here, but looking roughly at the efficacy numbers from the 18 month study, if you look at that 22 to 27 percent, if we kind of back that up to 12 months, and, again, careful how we put this into context, if we saw an efficacy rate kind of in the range of you know, roughly 15 to 20 percent, similar efficacy to what we are seeing with marketed drugs with a significantly better safety profile that we feel would be a significant win, and that is what we are hearing. And then any benefit kind of above that 20 percent would be total upside.

So we are trying to look at similar ish efficacy with a much improved safety profile, and I think that would be a, you know, that would be a significant win, if we saw that the efficacy side as well, we would like to see, directional trends in key biomarkers So I think the movement in the biomarkers, the trends we would see in some of these key biomarkers would tell us why we are seeing the efficacy in the clinical outcome measures. And the clinical outcome measures that are important to us would be you know, either or, the CDR Sum of Boxes or the iADRS. So these are the FDA-approved endpoints.

So that, again, that range in that 15-20% on either iADRS or CDR Sum of Boxes supported by directional trends and key biomarkers, which would really support the oligomer targeting thesis. Together with a much improved safety profile with ARIA rates at or close to placebo.

Analyst: Really helpful context. Thank you so much. Thank you, David.

Operator: Your next question comes from the line of Pete Stavropoulos with Cantor. Please go ahead.

Pete Stavropoulos: Hey, good afternoon, Neil and Larry, and thank you for taking my question. First question, part of it is sort of theoretical, but it would be great to hear your perspective. You do have these oligomers. They vary in molecular weight and size. Consisting of the same fragments. Does binding them necessarily mean neutralization? And can you speculate, you know, if antibody bound oligomer could still have neurotoxic effects And then sort of tying that back to the question of how much of an impact can the Fc isotype make, you know, especially IgG1 versus IgG2? Thanks.

Larry Douglas Altstiel: Okay. Thanks, Pete. it is a really interesting question. Does binding necessarily mean neutralization? I think that we have some hint from some of our preclinical studies in transgenic mice where treatment with PMN310 actually preserved memory acquisition and memory retrieval and also reduced the amount of inflammatory cytokines that were produced in the brain compared to untreated. So that does tell us. Gives us at least a hint that neutralizing the antibodies does have some effect in terms of in terms of activity. Now can the antibody-bound antibody actually still have or antigen-antibody complex still have toxic effect?

And I think the answer to that is unknown, but I do think that the antibody can stabilize the toxic oligomers and render them less toxic. However, if there is some ambiguity there, that really does speak to the importance of the IgG1 background. Because even if there is residual toxicity of the antigen-antibody complex, that removal ablates that effect. So that really does speak to the importance of what we have done here of having a very highly specific antibody that has a really, really you know, low kD. That means that it really binds to it, hangs on to that oligomer, does not let go, and then it is bound and removed by microglia.

So I think that they both work in concert that way.

Pete Stavropoulos: Alright. Thank you very much.

Operator: Your next question comes from the line of Ki Bin Kim with Chardan. Please go ahead.

Ki Bin Kim: Yeah. Thank you. Appreciating that your data is gonna be at 12 months. And there is some interpolation there. So, does the shape of the curve at 12 and the degree of separation, how much does that also impact your go/no-go decision?

Neil K. Warma: Yeah. I think it needs to be looked at kind of collectively, Ki Bin. Thanks for the question. You know, again, we are looking at it across the various, you know, the various kind of baskets of endpoints, if you will. And if we see again, it is 140 patients, 3-to-1 randomized. Like, I keep referencing that. I think if we see, you know, if we see that benefit coming in that range that we are saying you know, the separation we see between, active and placebo, combined with directional trends in those key biomarkers, I think that will be kind of really important signal. Again, we have also got.

You know, safety is gonna drive a lot of this as well. And then I think we sit with the FDA. Again, we plan with our end of phase 2 meeting once we collect all the data. And we sit with them, and we you know, we work with the FDA to demonstrate the benefit risk profile that we are taking forward. The rationale around reducing significantly, we feel, the number of MRIs that would be required We have also got our mechanism of action data Again, for the first time, we have got the assay that allows us to measure and detect levels of oligomers, and their reduction with PMN310.

And I think if you put those data points together, and really showcase that benefit risk change, then FDA should be in favor of allowing us to move forward with that next you know, ideally, registrational study.

Ki Bin Kim: Okay. And just if I could ask a follow-up on the sub q How confident are you based on any PK data you have that you will be able to formulate something equivalent, and how soon might that be ready? Will that be what you use in the pivotal?

Neil K. Warma: Yeah. it is a good question. I mean, goal is, I think, as we said, over the past few months now, we really initiated that sub q development program around the time of, the interim analysis. I think we were certainly given confidence by the interim data enough to the trigger to get the formulation around sub-Q going forward. It is our goal to bring the product to market as a sub-Q product. You know, we are looking to where the market's evolving to and where it will. It will have evolved in the next few years. Sub-Q is going to be important if we come to the market with you know, that benefit risk much improved.

We wanna be there with a very patient compliant product as well. So the early studies we have been working on are encouraging. Obviously, a lot's gonna depend on the results from the study around dose, but the kind of the PK that we are looking at early studies of this viscosity, the, you know, the volumes required for sub-Q and making it manageable and painless for the patient, are all going well. Our goal then is to once we get into that next ideally, the ideally the registration study, we would see ourselves running a sub-Q arm within that larger study. So this would be. You know, we.

We are not gonna slow down IV to let sub-Q catch up. So, no, Larry, it will be kind of a combined Yeah.

Larry Douglas Altstiel: I think, you know, when you talk about PK, we are 1 of the things we would like to get from the phase Ib study is a dose and exposure that gives us the maximum effect with respect to efficacy safety, and biomarkers, and so that would be an initial benchmark And by running the SubQ formulation, equivalency studies alongside phase 3. We have got a comparator arm so that we know what we have to hit with the with the sub q.

Neil K. Warma: Yeah. And so we are not slowing down the IV formulation, no. Far from it. But I think the sub q formulation will be able to catch up especially because we have these normative data from the phase 3 Yeah. So it is looking good, and it is. As I said, it is our goal to get to market with a sub-Q for sure.

Ki Bin Kim: Great. Thank you. Thanks, Ki Bin.

Operator: Your next question comes from the line of Fazia Ahmed with Brookline Capital Markets. Please go ahead.

Fazia Ahmed: Hi, team. Thank you for taking my question. My first question is with the upcoming CTAD presentation, focused on the 6-month interim safety and biomarker findings, could you give us some sense whether there will be additional insights from the data, or it could just be the similar. What we know that was disclosed in July?

Neil K. Warma: Hey, Fazia. Yeah. Thanks for joining. Thanks for the question. It will be, yeah, no additional information at CTAD. I mean, our goal at CTAD, as you rightfully say, is coming next week. When we are all there, we are presenting a poster which represents the interim analysis from last July. I think our goal there is just to continue to remind people of the differentiation of PMN310 remind them of the data that is been generated to date, including the interim analysis from, a couple of months ago, remind them of the, you know, of the data that is coming up, in a few months.

So it is really to kind of increase our exposure, You know, there is a--we are reaching out--very much a we are reaching out very much a clinical KOL driven event. We have got a number of interactions with KOLs, number of interactions with strategics and pharma companies. So it really is a way just to kind of yeah, reinforce our differentiation as a you know, I will not say the only, but certainly, in our view, 1 of the more exciting next-generation anti-amyloid therapies company, anti-amyloid drugs coming along.

So it is very much kind of, getting out in front of some of the KOLs and clinicians and pharma companies But, again, no new data will be will be presented on our part.

Larry Douglas Altstiel: I think there will be probably some contextual interest here given the results with ACU 3. And so we will be able to kind of reemphasize what we have had accomplished at the interim.

Fazia Ahmed: Thank you. And then I have 1 follow-up. Given that toxic oligomers are, like, structurally heterogeneous and, you know, they keep changing conformation. Can you share some thoughts on how PMN310, we know it recognizes a very specific conformation or specific epitope on that conformation. So as these oligomers are changing, how accessible that epitope is? To PMN310?

Larry Douglas Altstiel: Yeah. I think the. When the epitope is exposed, that is kind of the definition, in fact, of the toxic oligomers. As you point out, they are very plastic, poorly structured, and the epitope does appear on these. But as they become more structured, and less toxic, that epitope is buried inside fibrillar structures, i.e., ordered fibrils, and ultimately in plaque. So really, it is almost definitional that the that the aggregates of A-beta peptide that display this epitope do represent probably the bulk of the toxic oligomers that we are trying to eliminate. Mhmm.

Neil K. Warma: And they are consistent across kind of all brains and Alzheimer's brains we have tested. Hundreds Yeah. Hundreds. And that and that yeah, that binding, that conformational epitope is consistent across all Alzheimer's disease.

Larry Douglas Altstiel: And, of course, it is not just 1 patient or a handful of patients and also, too, you know, looking at low molecular weight fragments of brain homogenates or enhanced in oligomers, PMN310 removes the bulk of the oligomer material there.

Fazia Ahmed: Perfect. Thank you so much.

Operator: Thanks for the rest of the Your next question comes from the line of Bhuban Pachiakon with ROTH. Please go ahead.

Aaron: Hi. This is Aaron on for Bhuban. I just wanted to ask a question about Acumen's reported CSF antibody oligomer engagement, was assayed before by your company, and I wanted to know what kind of oligomer binding differences. Oligomer species binding differences you detected that may explain some of the clinical difference that has been observed. And if you will be reporting on any of these readouts in the oligomer species and free oligomers or antibody bound complexes in the readout later in 2027.

Larry Douglas Altstiel: I think that the acumen binding assay really represented a antibody saturation assay and the antibody being saturated with whatever PMR 8 ACU 3 binds, oligomers and a lot of other stuff as well. Now our assay is quite a bit different in that it measures the absolute concentrations of A-beta oligomers themselves. It is not inferential with respect to antibody saturation, but rather it measures the absolute concentration of oligomers in the cerebral spinal fluid.

We demonstrated this It was disclosed in a poster earlier this year, and at AAIC, and it is to the best of our knowledge, the first time that anybody's ever been able to do this, with this sort of subpicomolar kind of sensitivity that is required to detect not only the oligomers, but also our particular case, a dose response in a single you know, phase 1. A single dose phase 1 study. So that is what we will be reporting is the absolute decrement or change in oligomers as opposed to an antibody saturation.

Neil K. Warma: Yeah. that is why it kind of takes to the question. it is exciting for us as it. As I said, for the first time, we will be able to kind of show you know, hopefully, to prove our mechanism of action or our hypothesis that we have got an antibody that binds and clears oligomers. And up until now, we have never had an assay. Nobody's had an assay that was sensitive enough to measure these, the slow concentration of oligomers.

So again importantly, if we can show the safety biomarker movement clinical outcome measures and we can show precisely that it is due to the to the mechanism that we have proposed that will be very, very interesting not only for FDA, but also for us and pharma companies going forward if we can connect the mechanism of action. So we are excited to be able to present those data. And that assay, as Larry said, is being implemented into the phase 1b trial. So we will look at pre and post treatment of oligomer levels with PMN310.

Aaron: Great. Thank you, guys. Thanks.

Operator: Your next question comes from the line of Raghuram Selvaraju with H. C. Wainwright. Please go ahead.

Jade: Hi, Larry, Neil. This is Jade on for Ram. Thanks for taking our question. Hey, Jade. Hi, Jade. Hey. So you have, you know, previously discussed the potential for substantially less frequent MRI monitoring. Really, the question is, like, how and when would you evaluate whether this was reduced schedule is appropriate particularly in the ApoE4 homozygote?

Larry Douglas Altstiel: Well, right now, to date, we have seen or at least not to date, but in the 6 months, of analysis, we have not seen any ARIA-E And we have a normal distribution that 1 would expect with APOE genotypes, you know, in an Alzheimer's population. So there were a number of ApoE4 homozygotes, a high degree of ApoE4 heterozygotes. And, again, we saw no ARIA-E in this population, and a an ARIA-H rate that was consistent with what 1 would expect to see, in an untreated patient population, just the natural history.

Now with respect to, you know, how many MRI scans will be required as per the label, that is a discussion that we have to have with the agency, and we cannot really predict that you know, that they will say no more MRIs. We will just simply present the evidence as it. As we have it to date, and then as it accrues in subsequent studies, And I think if we see the same sort of trend, I think that we will be able to get rid of much of the MRI surveillance early on in the study.

Neil K. Warma: Yeah. And importantly too, Jade, I think. I believe that when you look at trontinemab that is, you know, using a shuttle here, and, you know, they have reduced, they have reduced their ARIA incidents significantly with the shuttle. Of course, shuttles bring their own complications. But interestingly, I believe in their phase 3 design, the agency has reduced the number of MRIs that they are allowed from 5 or 6 down to 3. So there is precedence coming you know, from the FDA that if you can reduce. You know, so I think it is important.

So we have been asked, is this class effect as an anti-amyloid targeting agent regardless of RA, you are you are gonna be given the same you know, whack on the risks that, that lecanemab and donanemab found, and I do not think that is the case. And I think trantorilimab shows that it is not a fast effect. And if we can come with an even cleaner safety profile, then there is a good chance that the MRI burden will be significantly reduced ideally, in the, you know, in the next you know, registration study that we wanna run.

And if we can consistently show, you know, low levels of RA going forward, we would expect that you know, some launch time it is not going to be on the label, which is which is which is important. So I think there is there is good signs that we can dramatically reduce the MRI because as I said in the in the piece earlier, it really is so cumbersome, burdensome for these patients and their caregivers to go multiple times a year for an MRI. You can imagine putting, you know, some of these patients who are not feeling too well into an MRI machine multiple times a year, is horrible. So ideally, that is 1 of our goals.

And I think that, you know, in addition to saving on you know, costs and health care costs, you know, the burden for the patient will be significantly reduced.

Larry Douglas Altstiel: Well, as Neil pointed out, there is FDA precedent. That we have seen that when you have the appropriate data, FDA will make a data driven decision and say, you know, the data suggests that you do not need all these scans. We think that we will come in with a safety data package that we will present to the FDA. I am not gonna presume what they will say. But we do have the precedent that they are Yeah. You know, flexible about you know, eliminating this apparent class effect Yeah. And having a data driven outcome.

Jade: Great. Thank you so much. And just quickly, just. I was trying to find the participant number for the plasma p-tau217 and the CSF MTBR-tau243 charts in the presentation, and I was not able to find them. Can you tell me?

Neil K. Warma: We did not provide-- I mean, These are-- when all patients you know, the total number of patients enrolled was a 144. The safety-evaluable number was 136. So when all those patients had reached the 6 month level, that is when we did our safety and biomarker analysis. We did not give specific numbers on MTBR or p tau as far as how many numbers of samples were collected from the patients. But, so we did not break that out in kind of finite detail. We will do all this kind of.

At the end of the study, we will put all the you know, all the patients and all the unblinded data, but we did not communicate that at the, at the interim level.

Jade: Okay. Great. Thank you so much. Looking forward to it. Yep. Yeah. Thanks.

Operator: Thank you. Your next question comes from the line of Pete Stavropoulos with Cantor Fitzgerald. Please go ahead.

Pete Stavropoulos: Yeah. Thank you for taking my follow-up. Assuming a positive outcome for the Phase Ib, and I understand that you need regulatory interactions, but, you know, are you sort of currently thinking about next steps Are you leaning towards a Phase 2b or a Phase 3? Or perhaps a Phase 2/3 adaptive design? And, you know, what will drive that decision? Thank you.

Neil K. Warma: Yeah. I think-- thanks, Pete. that is a good that is a good question. I mean, we are doing a lot of that discussion now, and, obviously, bringing somebody like Ivana Rubino onto the you know, into the onto the team allows us to think a little bit more, you know, deeply comprehensively around those questions. I think for us, you know, it could be. You know, our thinking is kind of a registrational type study, whether that is a Phase 3 or 2/3 adaptive. You know, we will see. We will kind of you know, the data will dictate some of that.

We are doing those kind of design elements now, kind of including a sub-Q arm as we talked about earlier. I think, you know, for us, we are being pretty bullish on you know, single registration study, the exact size and shape and cost, working on now, we have not really given any guidance. I think we will use, you know, Ivana's expertise, Larry's expertise to continue to you know, think through various, you know, various approaches, what we are doing, you know, taking advantage of this wave and enthusiasm around AI, being more careful how we do that.

But there is a lot of input we are getting from AI or we will get from AI around clinical trial designs, improving you know, improving efficiency and cost reduction. So there is a number of elements we are building into the design perspective. And I think as we go forward, get the data, sit down with the agency, you know, and get their feedback, that will kind of shape our final decision. Yeah.

Larry Douglas Altstiel: I think, Pete, I would not dwell too much on whether we would call it a phase 2 b, phase 3, or 3, but rather focus on a clinical trial that is going to stand as a registration quality study. Now there is a lot of different ways to get there, and as Neil pointed out, we are exploring them as we speak. But, it is that is that is our goal.

Neil K. Warma: Yeah. And, again, keep in mind, the reason you know, we designed such a comprehensive 1b study was to you know, to be able to step into a registrational-type study. I said we were pretty aggressive in numbers, and length of treatment in order to kind of you know, speed time to market and ideally get in front of the agency and propose a yeah, a registration study that gets us, you know, that gets us to commercial stage. Quicker than if we had done, you know, a smaller 1b study. So we are pleased with the design and, ideally, you know, the outcome will dictate a lot of things in a in a few months.

Pete Stavropoulos: Great. Thank you for that, and looking forward to the data in Q1. Very good. Thanks so much, Pete.

Operator: This now concludes our question and answer session. I would like to turn the floor back over to Neil for closing comments.

Neil K. Warma: Yes. Thanks, Kate, very much for your support. And thank you, everybody, for your time and your questions today. As I said, our focus really remains on patients and their families, and we are looking forward to showing in a few months that PMN310 could change the benefit risk balance in Alzheimer's disease and really help the patients who so urgently need it. So thank you so much for your attention and your support. We will update again soon.

Operator: Ladies and gentlemen, thank you for your participation. This does conclude today's teleconference. You may disconnect your lines, and have a wonderful day.

Larry Douglas Altstiel: Well done, Neil.

Neil K. Warma: Good job.

This article is a transcript of this conference call produced for The Motley Fool. While we strive for our Foolish Best, there may be errors, omissions, or inaccuracies in this transcript. Parts of this article were created using Large Language Models (LLMs) based on The Motley Fool's insights and investing approach. It has been reviewed by our AI quality control systems. Since LLMs cannot (currently) own stocks, it has no positions in any of the stocks mentioned. As with all our articles, The Motley Fool does not assume any responsibility for your use of this content, and we strongly encourage you to do your own research, including listening to the call yourself and reading the company's SEC filings. Please see our Terms and Conditions for additional details, including our Obligatory Capitalized Disclaimers of Liability.

The Motley Fool has no position in any of the stocks mentioned. The Motley Fool has a disclosure policy.